If given a lethal amount, it can last from minutes. Cyanide is able to kill so fast because the molecules are exceptionally small and can dispense throughout the entire body very quickly, affecting all major organs and tissues in a short amount of time.
It may not be an honorable way to go, but the effectiveness and the relatively quick process depending on the amount of cyanide administered , made an effective way to prevent captured spies giving up secrets to the enemy.
This site uses Akismet to reduce spam. Learn how your comment data is processed. Search for:. Download PDF. Like this: Like Loading Cyanide poisoning has been used in movies and real life, mostly associated with espionage.
But have you ever stopped to wonder what causes it to be lethal? September 22, September 22, Science Unfiltered Share. Low physiological levels nanomolar range of NO enhance cyanide inhibition of CcOX, whereas high levels of exogenous NO micromolar range antagonize the inhibition. Physiological NO directly inhibits CcOX to reduce oxygen consumption and indirectly activates mitochondrial signaling by altering the mitochondrial redox state and ROS production Cooper and Giulivi, As observed in this study, physiological levels of NO appear to enhance mitochondrial dysfunction produced by mitochondrial toxicants such as cyanide.
Gunasekar et al. Cyanide also increases levels of the NO metabolite, nitrite, in mescencephalic cells Prabhakaran et al. To explain the observed CcOX kinetics and respiratory interaction between cyanide and NO, a simplified model of competitive inhibition is inadequate Antonini et al. Binding of cyanide and NO to the CcOX binuclear center is complex and dependent on enzyme catalytic turnover, flux rate, and binuclear center redox status.
At the enzyme active site, cyanide and NO have different chemistry and different on and off rates that need to be considered in explaining their interaction Hill et al. As the fraction of CcOX in the reduced state increases, NO at micromolar concentrations competes with cyanide for binding to the reduced binuclear binding site to partly antagonize cyanide inhibition. This is consistent with observations of Pearce et al. It is also important to consider that inhibition by cyanide and NO are in competition with oxygen at the reduced heme a 3 site.
This partly explains why cyanide is such a rapid acting and potent intoxicant. Other reports suggest that excess CcOX prevents severe respiratory inhibition, as in the case of cyanide toxicity Davey et al.
It is concluded that N27 cells are more resistant to cyanide than primary neurons and that this may be explained by a higher level of anaerobic metabolism glycolysis and less dependence on mitochondrial aerobic respiration in the immortalized cells N However, it appears that the resistance of N27 to cyanide may be attributed in part to mitochondrial regulation since overexpression of uncoupling protein-2 in N27 cells leads to an enhanced cyanide cytotoxicity, similar to that observed in primary cells Zhang et al.
Many neurological disorders, including multiple sclerosis and Parkinson's disease, are characterized by substantial nitration of complexes I and IV. In these diseases, complexes I and IV are the primary sites of nitration, resulting in inhibition of oxidative phosphorylation Qi et al. Interestingly, acute cyanide toxicity has been linked to a delayed neuropathy resembling Parkinson's disease Rosenberg et al.
The resulting pathology may be due in part to cyanide-mediated nitration of complexes I and IV through upregulation of mtNOS. In a study by Broderick et al. It should be noted that NO generation undergoes a greater level of regulation in humans as compared to rodents Kroncke et al. Thus, caution should be taken when extrapolating NO-mediated pathology from rodent models to humans.
Current results provide valuable insight into cyanide-mediated inhibition of CcOX and explains the cyanide antidotal action of nitrite. Based on the present study, it appears that the anti-cyanide action of nitrite is due only in part to its ability to generate blood methemoglobin, a cyanide scavenger Way, We have provided in vivo evidence that the cyanide antidotal activity of nitrite may be related in part to NO generation Sun et al.
However, NO generated from nitrite may play a role in the antagonism of cyanide. The antagonism exceeded the cyanide scavenging capacity of the low methemoglobin levels. Furthermore, pretreatment with the methemoglobin-reducing agent, methylene blue, blocked methemoglobin generation but did not block ISDN's ability to antagonize cyanide.
The present study also provides a basis for the antidotal action of hyperbaric oxygen. Since cyanide is competitive with oxygen for binding to reduced heme a 3 , increased oxygen tension would facilitate displacement of cyanide to reactivate the enzyme. Thus, cyanide would in theory inhibit cellular respiration less effectively as O 2 tension increases.
Secondly, in the presence of the nitrite antidote, oxygen would alter the complex binding kinetics of both cyanide and NO, leading to reactivation of CcOX. The result would be increased CcOX activity. In summary, low endogenous nanomolar levels of NO enhance inhibition of CcOX by cyanide, whereas exogenous micromolar levels of NO antagonize cyanide. In turn, this excess NO contributes to cyanide inhibition of CcOX, which is competitive with oxygen at the enzyme's heme a 3 catalytic site.
These observations explain why cyanide is a rapid, potent intoxicant at the low oxygen tensions within mitochondria and provide mechanistic information on the antidotal action of the nitrite ion. L , PA In addition, the authors thank Dr Giselle Knudsen of Purdue University for her advice on kinetics and modeling. Google Scholar. Oxford University Press is a department of the University of Oxford.
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Volume Article Contents Abstract. Leavesley , Heather B. Oxford Academic. Li Li. Krishnan Prabhakaran. Joseph L. Gary E. Isom 1. Fax: E-mail: geisom purdue. Cite Cite Heather B. Select Format Select format. Permissions Icon Permissions. Abstract Acute cyanide toxicity is attributed to inhibition of cytochrome c oxidase CcOX , the oxygen-reducing component of mitochondrial electron transport; however, the mitochondrial action of cyanide is complex and not completely understood.
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